Based on the α7 nicotinic acetylcholine receptor(α7nAChR), this study examined how tetrahydropalmatine(THP) affected BV2 microglia exposed to lipopolysaccharide(LPS), aiming to clarify the possible mechanism underlying the anti-depression effect of THP from the perspectives of preventing inflammation and regulating polarization. First, after molecular docking and determination of the content of Corydalis saxicola Bunting total alkaloids, THP was initially identified as a possible anti-depression component. The BV2 microglia model of inflammation was established with LPS. BV2 microglia were allocated into a normal group, a model group, low-and high-dose(20 and 40 μmol·L~(-1), respectively) THP groups, and a THP(20 μmol·L~(-1))+α7nAChR-specific antagonist MLA(1 μmol·L~(-1)) group. The CCK-8 assay was used to screen the safe concentration of THP. A light microscope was used to examine the morphology of the cells. Western blot and immunofluorescence were used to determine the expression of α7nAChR. qRT-PCR was performed to determine the mRNA levels of inducible nitric oxide synthase(iNOS), cluster of differentiation 86(CD86), suppressor of cytokine signaling 3(SOCS3), arginase-1(Arg-1), cluster of differentiation 206(CD206), tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. The experimental results showed that THP at concentrations of 40 μmol·L~(-1) and below had no effect on BV2 microglia. THP improved the morphology of BV2 microglia, significantly up-regulated the protein level of α7nAChR, significantly down-regulated the mRNA levels of iNOS, CD86, SOCS3, TNF-α, IL-6, and IL-1β, significantly up-regulated the mRNA levels of Arg-1 and CD206, and dramatically lowered the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. However, the antagonist MLA abolished the above-mentioned ameliorative effects of THP on LPS-treated BV2 microglia. As demonstrated by the aforementioned findings, THP protected LPS-treated BV2 microglia by regulating the M1/M2 polarization and preventing inflammation, which might be connected to the regulation of α7nAChR on BV2 microglia.
Berberine Alkaloids/chemistry* ; alpha7 Nicotinic Acetylcholine Receptor/chemistry* ; Microglia/metabolism* ; Mice ; Animals ; Cell Line ; Corydalis/chemistry* ; Humans ; Molecular Docking Simulation ; Inflammation/drug therapy* ; Nitric Oxide Synthase Type II/immunology* ; Tumor Necrosis Factor-alpha/immunology*

Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Objective To establish the fingerprints of QiangliDingxuan tablets(QLDX),determine their pharmacody-namic indexes of vasodilation and study the spectrum-effect relationships between the chemical components of QLDX and the property of vasodilation.Methods The rate of vascular relaxation was used as an index to evaluate the extent to which QLDX relaxed isolated superior mesenteric artery ring.The Grey correlation degree and partial least square regression(PLSR)were used to analyze"spectrum-effect"correlations before components with greater contribution to drug efficacy were screened out.Results There were 21 common peaks in the HPLC fingerprint of QLDX,and the similarity exceeded 0.88.A comparison with the chromatogram of the reference substance revealed 14 characteristic peaks.Vasodilative experiments showed that all the 10 batches of samples had vasodilatory effects.The correlation between the 21 chromato-graphic peaks was greater than 0.73.PLSR showed that 11 components were positively correlated with the vasodilatory effect.Six known compounds included parishin A,parishin C,5-hydroxymethylfurfural,luteolin,Linarin and ligustrazine.Conclusion The vasodilatory effect of QLDX results from the combined action of multiple components.Parishin A,parishin C,5-hydroxymethylfurfural,luteolin,Linarin and ligustrazine are positively correlated with this effect,which may be the main pharmacodynamic substance basis of vascular relaxation.

This study was aimed at comparing performance differences among three metagenomic sequencing platforms,MGISEQ-2000,Illumina NextSeq 2000,and Ion GeneStudio S5 Plus,to optimize the sequencing process for trace samples.The three sequencing platforms were used to perform high-throughput sequencing on DNA standards and simulated samples.Through analysis of the quality of raw data and microbial detection capabilities,systematic differences among platforms were compared.The sequencing results were optimized for trace samples by incorporation of exogenous nucleic acids during the li-brary preparation process.In terms of data output per batch and base quality,MGISEQ-2000 surpassed the other two plat-forms.Illumina NextSeq 2000 had the lowest proportion of duplicate reads,whereas Ion GeneStudio S5 Plus had the highest proportion,and significant differences were observed across platforms(P＜0.001).In sequencing uniformity,MGISEQ-2000 and Illumina NextSeq 2000 were superior to Ion GeneStudio S5 Plus.MGISEQ-2000 provided a substantial advantage in microbial detection capability(P＜0.001),but the advantage diminished with decreasing bacterial fluid concentration.Ion GeneStudio S5 Plus had the shortest duration for single-batch sequencing.Moreo-ver,for trace samples with DNA content ≤0.05 ng,the experi-mental group(with added exogenous nucleic acids)achieved a higher number of reads than the control group(without exogenous nucleic acids),with a 11.09±8.03 fold increase.In conclu-sion,the different sequencing platforms each had advantages and disadvantages,thus allowing researchers to choose the appro-priate platform according to specific needs.Furthermore,the addition of exogenous nucleic acids improved the microorganism detection efficiency,and provided better support for subsequent diagnosis and evaluation of results.

Objective: To compare the efficacy of intravascular ultrasound (IVUS) and coronary angiography guided drug eluting stent (DES) implantation for the treatment of left main coronary artery (LMCA) lesions. Methods: Randomized controlled trials (RCT) and observational studies, which compared IVUS with coronary angiography guided DES implantation for the treatment of LMCA lesions published before August 2021 were searched in PubMed, Embase and Cochrane Library databases. Baseline data, interventional procedures and endpoint events of each study were collected. The primary endpoint was major cardiovascular adverse events (MACE), and the secondary endpoints were all-cause death, cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and target vessel revascularization (TVR). The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration Risk of Bias tool were used to evaluate the quality of the included studies. Results: Nine studies were included, including 3 RCT and 6 observational studies, with a total of 5 527 cases of LMCA. All the 6 observational studies had NOS scores≥6, and the 3 RCT had a low risk of overall bias. The results of meta-analysis showed that compared with coronary angiography guided group, MACE rate (OR=0.55, 95%CI 0.47-0.66, P<0.001), all-cause death (OR=0.56, 95%CI 0.43-0.74, P<0.001), cardiac death (OR=0.43, 95%CI 0.30-0.61, P<0.001), MI (OR=0.64, 95%CI 0.52-0.79, P<0.001), TLR (OR=0.49, 95%CI 0.28-0.86, P=0.013) and TVR (OR=0.77, 95%CI 0.60-0.98, P=0.037) were all significantly lower in the IVUS guided group. Conclusions: Compared with angiography guided, IVUS guided PCI with DES implantation in LMCA lesions could significantly reduce the risk of MACE, death, MI, TLR and TVR. IVUS is thus superior to coronary angiography for guiding PCI treatment among patients with LMCA.
Humans ; Coronary Artery Disease/complications* ; Coronary Angiography ; Drug-Eluting Stents/adverse effects* ; Treatment Outcome ; Percutaneous Coronary Intervention/methods* ; Ultrasonography, Interventional/methods* ; Risk Factors ; Myocardial Infarction/etiology*

This study aims to separate and characterize self-assembled nanoparticles(SAN) from Shaoyao Gancao Decoction(SGD) and determine the content of active compounds. Further, we aimed to observe the therapeutic effect of SGD-SAN on imiquimod-induced psoriasis in mice. The separation of SGD was performed by dialysis, and the separation process was optimized by single factor experiment. The SGD-SAN isolated under the optimal process was characterized, and the content of gallic acid, albiflorin, paeoniflorin, liquiritin, isoliquiritin apioside, isoliquiritin, and glycyrrhizic acid in each part of SGD was determined by HPLC. In the animal experiment, mice were assigned into a normal group, a model group, a methotrexate group(0.001 g·kg~(-1)), and SGD, SGD sediment, SGD dialysate, and SGD-SAN groups of different doses(1, 2, and 4 g·kg~(-1)) respectively. The psoriasis grade of mice was evaluated based on the pathological changes of skin lesions, the content of inflammatory cytokines, organ index and other indicators. The results showed that SAN obtained by centrifugation at 13 000 r·min~(-1) for 30 min was stable after dialysis for 4 times, which were uniform spherical nanoparticles with the particle size of(164.43±1.34) nm, the polydispersity index of(0.28±0.05), and the Zeta potential of(-12.35±0.80) mV. The active compound content accounted for more than 70% of SGD. Compared with the model group, SAN and SGD decreased the skin lesion score, spleen index, and inflammatory cytokine levels(P<0.05 or P<0.01) and alleviated the skin thickening and infiltration of inflammatory cells. However, the sediment group and the dialysate group had no obvious effect. SGD showed a good therapeutic effect on imiquimod-induced psoriasis in mice, and SAN demonstrated the effect equivalent to SGD in a dose-dependent manner. Therefore, we conclude that the SAN formed during decocting is the main active form of SGD, which can lower the levels of inflammatory cytokines, promote the normal differentiation of keratinocytes, and reduce the infiltration of inflammatory cells in the treatment of psoriasis lesions in mice.
Mice ; Animals ; Imiquimod ; Drugs, Chinese Herbal/pharmacology* ; Glycyrrhizic Acid ; Chromatography, High Pressure Liquid/methods*

Objective:To investigate the relationship between serum free triiodothyronine (FT 3) and the severity and prognosis of elderly patients with coronavirus disease 2019 (COVID-19). Methods:Clinical data of the elderly patients aged≥65 years old with COVID-19 who were admitted to the Ninth People′s Hospital of Wuxi from December 27, 2022 to January 18, 2023 were collected. The laboratory examinations of the non-severe and the severe/critical groups were compared. Patients were divided into group T1 (FT 3<2.51 pmol/L), group T2 (FT 3=2.51 to 2.95 pmol/L, ), and group T3 (FT 3>2.95 pmol/L) according to the FT 3 level. Independent sample t test was used for comparison between groups. Logistic regression analysis was performed to evaluate the risk factors for severe/critical disease, and to analyze the risk of severe/critical COVID-19 in elderly patients with different FT 3 levels. The receiver operator characteristic (ROC) curve was drawn to analyze the predictive value of FT 3 on the occurrence of severe/critical disease in patients. Kaplan-Meier survival curve and log-rank test were used to analyze the 30-day survival rate of elderly COVID-19 patients. Results:Among the 190 patients, the FT 3 level in the severe/critical group was (2.54±0.30) pmol/L, which was significantly lower than that in the non-severe group ((2.91±0.69) pmol/L), and the difference was statistically significant ( t=-3.42, P=0.001). Elevated serum FT 3 level was a protective factor for severe/critical disease in elderly COVID-19 patients (odds ratio ( OR)=0.139, 95% confidence interval ( CI) 0.034 to 0.577, P=0.007). There were 66 patients in the T1 group, 61 in the T2 group and 63 in the T3 group, respectively. After adjusted for sex, age, history of lung diseases, history of cardiac diseases, history of hypertension, history of diabetes mellitus, history of cerebral infarction, white blood cell count, lactate dehydrogenase, D-dimer, free thyroxine and thyrotropin, the risk of developing severe/critical disease in group T1 and group T2 were 10.982 folds and 3.695 folds of that in group T3, respectively (both P<0.05). The area under ROC curve of FT 3 of predicting severe/critical COVID-19 in the elderly patients was 0.731. The sensitivity and specificity were 0.733 and 0.659, respectively. The cut-off value was 2.53 pmol/L. The 30-day survival rate in patients with FT 3<2.53 pmol/L was significantly lower than that in patients with FT 3≥2.53 pmol/L ( χ2=13.49, P<0.001). Conclusions:The elevated level of FT 3 is a protective factor for progression to severe/critical disease in elderly patients with COVID-19. The evaluation of serum FT 3 could predict the severity and prognosis of elderly COVID-19 patients.

Silk fibroin is a natural polymer with certain water solubility, structural modification, good biocompatibility and biodegradability, which can be used as a drug delivery carrier material. As a promising drug delivery system, drug-loaded silk fibroin nanoparticles can control drug release, reduce toxicity and improve therapeutic effects. In this paper, the basic characteristics of silk fibroin, the preparation methods of drug-loaded silk fibroin nanoparticles and the application of silk fibroin in nanoparticulate drug delivery systems are reviewed, and on this basis, the further development of drug-loaded silk fibroin nanoparticles is prospected.

OBJECTIVE: To evaluate the diagnostic performances of salivary gland ultrasonography(SGUS)in Sjögren's syndrome(SS). METHODS: A total of 246 patients with dry mouth and/or eyes who were treated in the outpatient department and inpatient department of Rheumatology and Immunology Department of the Ninth People's Hospital, Shanghai Jiaotong University School of Medicine from December 2019 to January 2022 were collected. All patients received SGUS examination and scored by 2019 outcome measures in rheumatology clinical trial (OMERACT)ultrasonic scoring system.Their general information, unstimulated saliva flow rate(USFR), Schirmer test and serological test results were recorded. In the study, 193 cases had lip gland biopsy. The 2016 American College of Rheumatology(ACR)/ European League Against Rheumatism(EULAR)classification criteria were adopted as the diagnostic standard of SS. χ² test was used to compare the difference of salivary gland ultrasonic scores between the two groups. The receiver operating characteristic(ROC) curve was used to evaluate the accuracy of SGUS in diagnosing SS, and the disease characteristics of SGUS positive group and negative group in the SS patients were compared. RESULTS: A total of 175 patients were SS group according to the ACR/EULAR classification, and the remaining 71 patients were non-SS group.There was no significant difference in age [(54.2±11.8) years vs. (53.4±14.9) years, P=0.705] and female (94.4% vs.93.1%, P=1.000) between SS and non-pSS groups. A total of 109 patients were SGUS positive (≥ 2 points), of whom 104 patients met the SS diagnosis and 5 patients did not meet the SS diagnosis. The positive rate of SGUS in SS group was significantly higher than that in non-SS group (59.4% vs. 7.0%, P < 0.001). The accuracy of 2019 OMERACT ultrasonic scoring system to predict ACR/EULAR classification was good, with an area under the curve of 0.762 (95%CI 0.701-0.823). The absolute agreement between the SGUS outcome and ACR-EULAR classification was 69.1%(170/246), with a sensiti-vity of 59.4%(104/175), specificity of 93%(66/71), positive predictive value of 95.4%(104/109) and negative predictive value of 48.2% (66/137). A total of 81 patients were positive SGUS combined with anti-SSA antibody, 100% (81/81) fulfilled the ACR-EULAR criteria, 85 patients were negative SGUS and anti SSA antibody, and 60 patients(70.6%, 60/85) did not fulfil the ACR-EULAR criteria. SGUS positive group had higher antinuclear antibody(ANA) positive rate(83.1% vs. 98.1%, P < 0.001) in the patients with SS. CONCLUSION The OMERACT ultrasonic scoring system has high diagnostic value in SS. The combination of SGUS and anti-SSA antibody can improve the diagnostic value.
Humans ; Female ; Adult ; Middle Aged ; Aged ; Sjogren's Syndrome/diagnostic imaging* ; Sensitivity and Specificity ; China ; Salivary Glands/pathology* ; Ultrasonography/methods*